Improving staffing and quality: a nursing support team.
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Humans↗
Biomedical subjects
A Jackson
Publications and source records attributed to A Jackson.
Attenuation of the lordosis-inhibiting effects of 8-OH-DPAT by TFMPP and quipazine.
Regularly cycling, proestrous female rats received infusions of 200 ng of the serotonin (5-HT) 1A receptor agonist, (+/-) 8-hydroxy 2-(di-n-propylamino) tetralin-HBr (8-OH-DPAT), or 200 ng 8-OH-DPAT and 1000 or 2000 ng of N-(3-trifluoro-methylphenyl) piperazine hydrochloride (TFMPP) or 2-(1-piperazinyl) quinoline dimaleate (quipazine). Infusions were made bilaterally into the ventromedial nucleus of the hypothalamus (VMN). Animals receiving 200 ng 8-OH-DPAT exhibited a decline in lordosis behavior following infusion. Rats receiving 8-OH-DPAT and 1000 or 2000 ng quipazine or TFMPP were protected from the lordosis-inhibiting effects of 8-OH-DPAT, alone. Although both quipazine and TFMPP act on multiple 5-HT receptors, they overlap in their agonist action at 5-HT2 receptors. Consequently, these results provide further evidence supporting the contention that within the VMN, both 5-HT1A and 5-HT2 receptor subtypes contribute to the modulation of lordosis behavior in the female rat. The data are discussed in terms of the relative potency of 5-HT at 5-HT receptors mediating inhibition and facilitation of lordosis behavior.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
The extravesicular domain of synaptotagmin-1 is released with the latent fibroblast growth factor-1 homodimer in response to heat shock.
The heparin-binding fibroblast growth factor (FGF) prototypes lack a classical signal sequence, yet their presence is required in the extracellular compartment for the activation of cell-surface receptor-dependent signaling. Early studies with FGF-1 demonstrated its presence in bovine brain as a novel high molecular weight complex, and subsequent studies identified a second heparin-binding protein that co-purified with FGF-1. Polypeptide sequence analysis revealed that this heparin-binding protein corresponded to the extravesicular domain of bovine synaptotagmin (Syn)-1, a transmembrane component of synaptic vesicles involved in the regulation of organelle traffic. Since FGF-1 is released in response to heat shock as a mitogenically inactive Cys-30 homodimer, we sought to determine whether this heparin-binding protein was involved in the release of FGF-1. We report that a proteolytic fragment of the extravesicular domain of Syn-1 is associated with FGF-1 in the extracellular compartment of FGF-1-transfected NIH 3T3 cells following temperature stress. By using heparin-Sepharose affinity to discriminate between the monomer and homodimer forms of FGF-1 and resolution by conventional and limited denaturant gel shift immunoblot analysis, it was possible to identify FGF-1 and Syn-1 as potential components of a denaturant- and reducing agent-sensitive extracellular complex. It was also possible to demonstrate that the expression of an antisense-Syn-1 gene represses the release of FGF-1 in response to heat shock. These data indicate that FGF-1 may be able to utilize the cytosolic face of conventional exocytotic vesicles to traffic to the inner surface of the plasma membrane where it may gain access to the extracellular compartment as a complex with Syn-1.
3T3 Cells↗
Synaptotagmin-1 is required for fibroblast growth factor-1 release.
By using p65 synaptotagmin-1 and fibroblast growth factor (FGF)-1:beta-galactosidase (beta-gal) NIH 3T3 cell co-transfectants, we demonstrate that a proteolytic fragment consisting of the extravesicular domain of synaptotagmin-1 is released into the extracellular compartment in response to temperature stress with similar kinetics and pharmacological properties as FGF-1:beta-gal. Using a deletion mutant that lacks 95 amino acids from the extravesicular domain of synaptotagmin-1, neither synaptotagmin-1 nor FGF-1:beta-gal are able to access the stress-induced release pathway. Furthermore, the p40 extravesicular fragment of synaptotagmin-1 is constitutively released in p40 synaptotagmin-1 NIH 3T3 cell transfectants, and this release is potentiated when the cells are subjected to temperature stress. These data demonstrate that the p40 fragment derived from synaptotagmin-1 is able to utilize the FGF-1 non-classical exocytotic pathway and that the release of FGF-1 is dependent on synaptotagmin-1.
3T3 Cells↗
S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro.
We have previously characterized the release of the signal peptide sequence-less fibroblast growth factor (FGF) prototype, FGF-1, in vitro as a stress-induced pathway in which FGF-1 is released as a latent homodimer with the p40 extravesicular domain of p65 synaptotagmin (Syn)-1. To determine the biologic relevance of the FGF-1 release pathway in vivo, we sought to resolve and characterize from ovine brain a purified fraction that contained both FGF-1 and p40 Syn-1 and report that the brain-derived FGF-1:p40 Syn-1 aggregate is associated with the calcium-binding protein, S100A13. Since S100A13 binds the anti-inflammatory compound amlexanox and FGF-1 is involved in inflammation, we examined the effects of amlexanox on the release of FGF-1 and p40 Syn-1 in response to stress in vitro. We report that while amlexanox was able to repress the heat shock-induced release of FGF-1 and p40 Syn-1 in a concentration-dependent manner, it had no effect on the constitutive release of p40 Syn-1 from p40 Syn-1 NIH 3T3 cell transfectants. These data suggest the following: (i) FGF-1 is associated with Syn-1 and S100A13 in vivo; (ii) S100A13 may be involved in the regulation of FGF-1 and p40 Syn-1 release in response to temperature stress in vitro; and (iii) the FGF-1 release pathway may be accessible to pharmacologic regulation.
Administration, Topical↗
Dose-dependent effects of estradiol benzoate on 5-HT1A receptor agonist action.
The lordosis-inhibiting effects of the 5-HT1A receptor agonist, (+/-)8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), were examined in ovariectomized rats, hormone primed with 2.5, 7.5, or 25 micrograms estradiol benzoate plus 500 micrograms progesterone. 8-OH-DPAT (50, 100 or 200 ng per bilateral site) infused into the ventromedial nucleus of the hypothalamus (VMN), inhibited lordosis behavior in all hormone-treated conditions. However, animals primed with 2.5 micrograms estradiol benzoate were significantly more affected by the infusion than rats primed with 7.5 or 25 micrograms of the hormone. These findings strengthen prior speculations that 5-HT1A receptor function is modulated by estrogen.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21.
Deletion of the long arm of chromosome 6 (6q) is one of the most common chromosomal abnormalities in human hematological malignancies. Two distinct regions of minimal deletion have been identified by loss of heterozygosity studies at 6q25 to 6q27 (RMD-1) and at 6q21 to 6q23 (RMD-2), suggesting the presence of one or more tumor suppressor genes. We have cloned sequences within RMD-2 and screened for novel genes using a combination of direct sequencing, cDNA library screening, and exon trapping. Sequences generated from a cosmid fragment, mapping within RMD-2, showed homology to the Drosophila tailless gene (tll). The human homologue of the Drosophila tailless gene (human tlx; MGMW-approved symbol, TLX) was subsequently cloned from a fetal brain cDNA library. The gene is a member of the steroid nuclear receptor superfamily and is homologous to tll genes from other species that are involved in brain development. TLX is predominately expressed in the brain and maps to RMD-2 at 6q21 between DNA markers FYN and D6S447, in a YAC clone that also contains marker D6S246. The contributions of this gene to human B-cell leukemia and to brain development are unknown at present.
Amino Acid Sequence↗
A multifaceted study of human papillomavirus and prostate carcinoma.
BACKGROUND: The presence of human papillomavirus (HPV) in the prostate and its role in prostate carcinoma are in dispute. To address these issues, two laboratories with extensive HPV experience were selected to test specimens from two populations at different risk for prostate carcinoma, using three different polymerase chain reaction (PCR) assays and two serologic assays for HPV. METHODS: The cases were comprised of 51 African-American (men at high risk for prostate carcinoma) and 15 Italian (men at intermediate risk for prostate carcinoma) men with prostate carcinoma. Controls were 108 African-American men and 40 Italian men with histologically proven benign prostate hypertrophy (BPH). Prostate tissue was obtained from each patient at surgery and immediately frozen in liquid nitrogen. The PCR primer sets included two (MY09/MY11 and GP5+/ GP6+) that amplify different regions of L1 and a third (WD66,67,154/WD72,76) targeted to E6. Sensitivity in the 2 L1 PCR assays was shown to be 1 HPV DNA genome per 100 cells. Serum antibodies to HPV-16 and HPV-11 virus-like particles (VLPs) were detected using enzyme-linked immunosorbent assays. RESULTS: All available prostate carcinoma tissue specimens (n = 63) and BPH specimens from selected controls (n = 61) were tested by PCR. Human beta-globin DNA could be amplified from all specimens except three carcinomas, but no HPV DNA was detected in any case or control specimens by MY09/MY11 or E6 PCR. Microdissection of 27 carcinoma specimens was conducted to minimize nontumor DNA, but results remained negative by MY09/MY11 and GP5+/GP6+ PCR. In addition, serum specimens in cases (n = 63) and controls (n = 144) showed no differences in their responses against HPV-16 (P = 0.54) or HPV-11 VLPs (P = 0.64). CONCLUSIONS: The findings suggest that HPV is not associated with prostate carcinoma, and that HPV DNA is not at all common in the prostate glands of older men.
Aged↗
Can primary prevention or selective screening for melanoma be more precisely targeted through general practice? A prospective study to validate a self administered risk score.
OBJECTIVES: To establish whether a questionnaire incorporating MacKie's risk factor flow chart can identify patients at high risk for melanoma so that they can be targeted for primary and secondary prevention. To validate the risk score derived from the questionnaire and test the feasibility of self completion by comparing patients' self reported skin characteristics with a skin examination performed by an experienced general practitioner. DESIGN: Prospective questionnaire survey followed by a comparative study. SETTING: 16 randomly selected group practices in a health district in Cheshire, United Kingdom. SUBJECTS: Questionnaire survey--3105 consecutive patients aged 16 years and over attending for a primary care consultation; comparative study--a self selected subsample of 388 of the 3,105 patients. MAIN OUTCOME MEASURES: MacKie risk group for melanoma. Comparison of high risk skin characteristics reported by patients and those noted during a skin examination by a doctor (kappa statistic). RESULTS: 4.3% of patients (87% women) were in the highest risk group and 4.4% (79% men) were in the second highest risk group, as defined by the MacKie score. Agreement between patients' self appraisal of skin characteristics and clinical skin examinations was reflected in kappa values of 0.67 for freckles, 0.60 for moles, and 0.43 for atypical naevi. CONCLUSION: This questionnaire helped to identify a group at high risk for melanoma. Furthermore, good agreement was found when the patient's risk scores were compared with results of the clinical skin examination. This risk score is potentially useful in targeting primary and secondary prevention of melanoma through general practice.
Age Distribution↗
Is subcortical disease associated with a poor response to antidepressants? Neurological, neuropsychological and neuroradiological findings in late-life depression.
BACKGROUND: Late-life depression is associated with increased subcortical white matter hyperintensities. There is some evidence that they are associated with a poorer response to acute treatment. Neurological signs and neuropsychological dysfunction are further evidence of abnormalities in the brain, but they have not been studied in relation to therapy resistance. METHODS: A prospective study of 24 normal controls and 75 consecutive elderly (aged 65 to 85) patients with DSM-III-R major depression entered a naturalistic study of treatment. Assessment of response to monotherapy and then lithium augmentation or ECT created three outcome groups. Investigations included magnetic resonance brain imaging, neuropsychological and neurological examination. RESULTS: Response to monotherapy within 12 weeks was shown by 42.7%, a further 37.3% responded to lithium augmentation or ECT within 24 weeks and 20% had responded poorly to all treatments at 24 weeks. Subcortical hyperintensities were significantly increased in the more resistant patients. These included confluent deep white matter, multiple (> 5) basal ganglia lesions and pontine reticular formation lesions. Most of the neuropsychological impairment was restricted to the resistant groups and was of a subcortico-frontal type. Extrapyramidal, frontal and pyramidal neurological signs characterized the resistant groups. The combination of extrapyramidal signs, pyramidal tract signs and impairment of motor hand sequencing strongly predicted resistance to 12 weeks of antidepressant monotherapy with 89% sensitivity and 95% specificity. CONCLUSION: In late-life depression a poor response to antidepressant monotherapy can be expected in those patients with a frontal lobe syndrome, extrapyramidal signs or if MRI T2-weighted lesions are present in both the basal ganglia and the pontine reticular formation.
Aged↗
Anatomical variation of cerebral venous drainage: the theoretical effect on jugular bulb blood samples.
Recent studies have demonstrated significant variation in bilateral jugular venous oxygen saturation measurements which may be of clinical significance. We have therefore measured variations in normal dural sinus venous drainage to assess the possible effects of normal anatomical variations on measured jugular venous oxygen saturation. Normal volunteers (n = 25) were imaged using magnetic resonance venography to demonstrate variations in venous anatomy. Flow was measured in the superior sagittal sinus and bilaterally in the transverse sinus, sigmoid sinus proximal to the jugular bulb and proximal jugular vein using phase difference magnetic resonance imaging. Examination of magnetic resonance venogram images showed considerable variability in the symmetry of transverse sinus flow. Complete absence of one transverse sinus was seen in four cases and significant asymmetry in the size of the transverse sinuses was present in 13. Quantitative flow studies demonstrated that the ratio of superior sagittal sinus to combined jugular bulb flow showed remarkably little variation (0.46 +/- 0.06). Measurements of transverse sinus flow showed significant asymmetry (< 40% of superior sagittal sinus flow in one transverse sinus) in 21 of 25 volunteers. The effect of the observed asymmetry on jugular venous oxygen saturation was modelled based on the assumption of either a supratentorial or infratentorial lesion. This model predicted significant asymmetry in jugular venous oxygen saturation measurements (> 10%) in 65% of cases with a supratentorial lesion which is in close agreement with clinical observations. This study suggests that normal variations in venous drainage may account for observed asymmetry in jugular venous oxygen saturation measurements.
Adult↗
Role of acetylcholine receptors and dopamine transporter in regulation of extracellular dopamine in rat carotid body cultures grown in chronic hypoxia or nicotine.
Using dissociated rat carotid body (CB) cultures, we compared levels of extracellular dopamine (DA) around oxygen-sensitive glomus cells grown for approximately 12 days in normoxia (Nox; 20% O2), chronic hypoxia (CHox; 6% O2), or chronic nicotine (CNic; 10 microM nicotine, 20% O2), with or without acetylcholine (ACh) receptor (AChR) agonists/antagonists and blockers of DA uptake. In Nox cultures, extracellular DA, determined by HPLC and normalized to the number of tyrosine hydroxylase-positive glomus cells present, was augmented by acute (approximately 15-min) exposure to hypoxia (5% O2; approximately 6x basal), high extracellular K+ (30 mM; approximately 10x basal), nomifensine (1 microM; a selective DA uptake inhibitor; approximately 3x basal), and nicotine (100 microM; approximately 5x basal), but not methylcholine (300 microM; a specific muscarinic agonist). In contrast, in CHox cultures where basal DA release is markedly elevated (approximately 9x control), the stimulatory effect of high K+ (3-4x basal) and acute hypoxia (approximately 2x basal) on DA release persisted, but nicotine and nomifensine were no longer effective and methylcholine had a partial inhibitory effect. In CNic cultures, basal DA levels were also elevated (approximately 9x control), similar to that in CHox cultures; however, although acute hypoxia had a stimulatory effect on DA release (approximately 2x basal), nicotine, nomifensine, and high K+ were ineffective. The elevated basal DA in both CHox and CNic cultures was attenuated by acute or chronic treatment with mecamylamine (100 microM), a nicotinic AChR (nAChR) antagonist. In addition, long-term (16-h), but not acute (15-min), treatment with the muscarinic antagonist atropine (1 microM) produced an additional enhancement of basal DA levels in CHox cultures. Thus, after chronic hypoxia or nicotine in vitro, extracellular DA levels around CB chemoreceptor cell clusters appear to be set by a variety of factors including released ACh, positive and negative feedback regulation via nAChRs and muscarinic AChRs, respectively, and modulation of DA transporters. These results provide insight into roles of endogenous transmitters in the adaptation of CB chemoreceptors to chronic hypoxia and suggest pathways by which neuroactive drugs, e.g., nicotine, can interfere with the protective chemoreflex response against hypoxia.
Animals↗
Psychological and socio-medical aspects of HIV/AIDS: a reflection on publications in AIDS care (1989-1995).
It is necessary to consider the content and methods of AIDS social research publications for these represent research advances as well as current issues of concern for practitioners, communities and researchers alike. This article critically examines some of the research that has been conducted to date into social aspects of HIV and AIDS. It quantifies the content and major methodological style of publications in the journal AIDS Care from 1989 to 1995. The most commonly published topic area in AIDS Care, during this period was cultural and demographic issues (15.9%), followed by issues pertinent to the psychological impact of HIV (13.6%), sexual behaviour and condom use (11.3%) and policy and services (9.5%). Research and measurement issues were the least examined content area in AIDS Care 1989-1995 (2.6%). This article discusses possible variables that influence the style and topics that are published in AIDS Care and makes suggestions for authors to consider before embarking on future research projects or publications.
Acquired Immunodeficiency Syndrome↗
Evidence for the existence of a novel pregnancy-associated soluble variant of the vascular endothelial growth factor receptor, Flt-1.
Angiogenesis is essential in physiological processes including ovulation, implantation and pregnancy. One of the most potent regulators is the cytokine vascular endothelial growth factor (VEGF). We provide evidence for a novel pregnancy-associated soluble variant of the VEGF receptor Flt-1. VEGF ranged from undetectable to 157.3 pg/ml (mean 49.9 pg/ml, SD 48.4 pg/ml) in plasma samples from normal volunteers (n = 10), but was undetectable in plasma from pregnant women (n = 12) and amniotic fluid (n = 10). Recoveries of spiked VEGF were poor in pregnancy-related samples, indicating the presence of VEGF-binding activity which was confirmed using biosensor and chromatographic techniques. Partial purification and protein sequencing indicated a novel soluble form of Flt-1 with a subunit size of 150 kDa. Normally present as a multimeric structure of approximately 400-550 kDa, complexes of 600-700 kDa were formed following binding of multiple VEGF molecules. Reverse transcriptase polymerase chain reaction of Flt-1 in placenta, amnion, chorion, human umbilical vein endothelial cells and cord blood samples produced bands of the predicted sizes but failed to identify any additional RNA species, and possible reasons for this are discussed. Soluble Flt-1 may be important in regulating the actions of VEGF in angiogenesis and trophoblast invasion and may have therapeutic implications in diseases with inappropriate angiogenesis such as proliferative retinopathies and cancer.
Amino Acid Sequence↗
AMPA receptors and motivation for drug: effect of the selective antagonist NBQX on behavioural sensitization and on self-administration in mice.
A series of experiments was carried out in which the potency of the selective alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA)-receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) (10-100 mg/kg) on locomotor activity was investigated, in mice. NBQX reduced all forms of activity studied, but its potency to do so varied according to the conditions of the experiment. The smallest dose of NBQX significantly reducing spontaneous or cocaine-induced activity was 100 mg/kg. Mice that had been repeatedly treated with 16 mg/kg cocaine once per week, for 7 weeks, showed a sensitized locomotor response to a challenge dose of cocaine (16 mg/kg). NBQX reversed the sensitized response at 30 and 100 mg/kg. The pattern of results obtained leaves open the role that AMPA-receptors may have in the expression of behavioural sensitization. In two further experiments, mice were trained to self-administer cocaine (30 micrograms per reinforcer) via intravenous catheters, using an operant lever pressing technique. When the amount of cocaine per reinforcer was doubled (to 60 micrograms) or halved (to 15 micrograms) the mice adapted lever pressing rates to maintain some constancy of self-dosing (but not at 7.5 micrograms per reinforcer) and when saline was substituted for cocaine, response rates increased considerably (extinction bursting). NBQX (10 and 30 mg/kg) reduced the self-administration of 30 micrograms reinforcers of cocaine, but only during the first 30 min of the test session. There was no evidence that NBQX specifically antagonized the reinforcing effect of cocaine, as responding was similarly reduced on both the reinforced and the non-reinforced lever, nor did the response to NBQX mimic behaviour seen following changes in the concentration of the reinforcer. The results of the locomotor experiments and the self-administration experiments are discussed together, in terms of current hypotheses about glutamatergic mechanisms involved in motivation for drug.
Animals↗
Use of computed tomography to investigate cheek tooth abnormalities in chinchillas (Chinchilla laniger)
Computerised tomographic scanning was used to investigate tooth structure in chinchillas (Chinchilla laniger), both cheek tooth crown and root abnormalities being common in this species. This paper describes a common form of dental disease affecting species with continuously growing teeth, with particular reference to the chinchilla, and confirms the potential role of computed tomography (CT) in its early diagnosis. CT imaging is compared with previously available methods of investigation which frequently fail to detect early pathological changes.
Animals↗
Optic neuritis: MR imaging with combined fat- and water-suppression techniques.
PURPOSE: To examine the benefits of combined fat- and water-suppressed T2-weighted magnetic resonance (MR) images in the diagnosis of optic neuritis. MATERIALS AND METHODS: MR imaging was performed with a 1.5-T unit in five healthy volunteers and 18 patients (21 nerves). All patients had abnormalities of visual evoked potentials and fulfilled the clinical criteria for the diagnosis of optic neuritis. Imaging was performed within 4 weeks of diagnosis (n = 12) or between 3 and 6 months after diagnosis (n = 6). Coronal images were obtained throughout the course of the optic nerve with use of three sequences: (a) short inversion time inversion recovery with fast spin-echo (SE) acquisition, (b) selective partial inversion-recovery (SPIR) prepared T2-weighted fast SE acquisition, and (c) SPIR-fluid-attenuated inversion recovery (FLAIR) with fast SE acquisition. RESULTS: Neuritic segments were demonstrated in all 21 symptomatic nerves. The extent of neuritic involvement (number of images showing abnormality) was significantly greater with the SPIR-FLAIR sequence (P < .01). The contrast ratio between neuritic optic nerve and orbital fat, normal nerve, and cerebral spinal fluid was significantly greater with SPIR-FLAIR than with the other sequences (P < .001). SPIR-FLAIR images also improved demonstration of optic nerve atrophy in chronic neuritis when compared with the other sequences. CONCLUSION: The SPIR-FLAIR sequence offers important advantages over current methods in the demonstration of optic neuritis.
Adult↗
Neutral amino acid uptake by the microvillous plasma membrane of the human placenta is inversely related to fetal size at birth in normal pregnancy.
Understanding the physiological regulation of fetal growth is important, as normal variations in size at birth relate to differences in neonatal and adult health. Although fetal growth directly reflects net placental transfer, little is known about how normal fetal growth relates to the transfer capabilities of the placental epithelium, the syncytiotrophoblast. The Na(+)-dependent and Na(+)-independent uptakes of methylaminoisobutyric acid (MeAIB) by vesicles prepared from the syncytiotrophoblast microvillous plasma membrane give measurements of system A neutral amino acid transporter activity and diffusive permeability, respectively. In 62 normal pregnancies, we related vesicle MeAIB uptakes to neonatal anthropometry. Smaller babies with a lower abdominal circumference had higher placental system A activity per mg membrane protein (P = 0.004); activity rose from 0.020 to 0.043 nmol/30 sec/mg protein as abdominal circumference fell from 34.6 cm or more to 32.0 cm or less. Within the normal range of fetal and placental size, this may reflect a tendency toward compensatory up-regulation of the placental system A transporter in smaller babies. Babies with a lower abdominal circumference also had higher Na(+)-independent MeAIB uptakes (P = 0.0005); this could reflect important compositional changes in the microvillous plasma membrane, leading in vivo to increased back-diffusion of amino acids out of the syncytiotrophoblast.
Adult↗